The Epidermal growth factor (hereinafter sometimes referred to as "EGF") is a peptide having a molecular weight of about 6,000, has proliferation-stimulating function for a wide variety of mammalian cells, and is contained in body fluid of all mammals. Since EGF is contained in breastmilk in a relatively high concentration, general attention is attracted by the relationship between EGF and growth and development of a newborn (neonate in the case of an animal), and among others, the effect of EGF on the development of digestive tract of neonatal rat and mouse has been studied. For example, it has been clarified that feeding a neonatal rat with an artificil milk added with EGF accelerate synthesis of DNA in the small intestine [C. L. Berseth: American Journal of Physiology, Vol. 253, p. G662, 1987], and that it increases the wet weight of stomach [J. Falconer: Biology of the Neonate, Vol. 52, p. 347, 1987, and E. V. O'Loughlin, et al: American Journal of Physiology, Vol. 249, p. G674, 1985]. It has also been demonstrated that administration of EGF to a neonatal rat accelerates development functions of the small intestine and mucosa thereof [C. Malo, et al: Gastroenterology, Vol. 83, p. 23, 1982, and Y. Oka, et al: Endocrinology, Vol. 112, p. 940, 1983].
There are known some cases of application of EGF for therapy of digestive tract diseases in accordance with the findings as described above. A recent case is reported where administration of EGF to an eight month old infant suffering from necrotic inflammation of small intestine (necrotinsing enteritis) led to recovery of fataldamages to the digestive tract [P. E. Sullivan, et al: Lancet, Vol. 338, p. 53, 1991], demonstrating clinical effectiveness of EGF.
The effect and the action mechanism of EGF on cultured cells have widely been studied to date since discovery of EGF in 1962. Regarding digestive tract cells, it has now been clarified that DNA synthesis in intestine apithelial cells is accelerated by EGF, and this action is caused via an EGF receptor presentin the cytoplasmic membrane [M. E. Forgue Lafite, et al: FEBS Letter, Vol. 114, p. 243, 1980; and N. Gallo-payet, et al: Endocrinology, Vol. 116, p. 194, 1985].
Sice usefulness of EGF for activating the digestive trtact has been revealed, blending of EGF into powder milk for infant was proposed (Japanese Patent Provisional Publication No. 62-228,225; and Japanese Patent Provisional Publication No. 1-148,146). More specifically, because digestive tract cells are not matured, a newborn is susceptible to easy entry of various bacteria and antigens through the digestive tract, and furthermore because of an incomplete immunological function, a newborn is sensible to infectious diseases. Therefore, with a view to promoting growth or proliferation of digestive tract cells, accelerating development of the digestive tract functions, and preventing ingression of bacteria, it was proposed to blend EGF into powder milk for infant.
Breastmilk contains, in addition to EGF, other substances showing proliferation stimulating function. Lactoferrin (hereinafter sometimes referred to as "Lf") is an iron-binding protein having a molecular weight of about 80,000 contained in a very large quantity in breastmilk, and has been known to exhibit an antimicrobial activity against detrimental micro-organisms such as Escherichia coli, candida, clostridium and Staphylococcus [Journal of Pediatrics, Vol. 91, p. 1, 1979; and Journal of Dairy Science, Vol. 67, p. 60, 1981]. The known functions of Lf and its hydrolysate thereof include antimicrobial activity and inhibition of tyrosinase activity (European Patent Provisional Publication No. 438,750); prevention of adherence of pathogen (Japanese Patent Provisional Publication No. 3.multidot.220,130); and antiviral activity (Japanese Patent Provisional Publication No. 1 233,266). More recently, it has been clarified that DNA synthesis of rat small intestine epithelial crypt cells is accelerated by Lf [B. L. Nichols, et al: Pediatric Research, Vol. 21, p. 563, 1987], and Lf is attracting the general attention as a new proliferation stimulating factor in breastmilk. From the same point of view as that of EGF, blending of Lf to an infant food composition is also proposed (Japanese Patent Provisional Publication No. 1-93,534).
As described above, EGF and Lf have so far been used singly in powdery milk for infant and infant food compositions. The number of persons suffering from digestive tract diseases such as gastric ulcer is on the other hand increasing under the effect of mental stress and it is needless to mention that elderly persons of advanced age tend to have decreased functions of digestive tract. Under such circumstances, it is considered significant to effectively utilize the results of research on the above mentioned powdery milk for infant and the like for prevention and therapy of digestive tract diseases of adults and for activating digestive tract cells functionally becoming poorer with age.
Unlike digestive tract cells of a newborn or an infant in the midst of growth, single administration of EGF or Lf cannot bring about a remarkable effect for digestive tract cells of an adult because the cells of an adult have already discontinued the rapid proliferation or the rapid growth which is observed in the case of newborn or an infant. In order to use EGF or Lf for the above mentioned purpose, it is necessary to intensify activity thereof by some method or other. Such a method has not however been known conventionally, and no attempt has as yet been made to try simultaneous use of EGF and Lf. Simultaneous use of EGF and Lf has not been tried since synergistic effect could not be expected from the simultaneous use because of the difference in action mechanism as a cell proliferation stimulating factor (for example, Japanese Patent Provisional Publication No. 1-93,534).